Given the current trend in medicine—dictated by the requirement of national health services and private insurance companies to limit medication costs—for carrying out the greatest possible number of operations without general anaesthetic and therefore without patient hospitalisation, there is current interest in further developing regional and local, rather than general, anaesthetic techniques. Given recent developments and the comparative progress achieved, regional and local anaesthesias prove to be even safer than general anaesthesia, which is hence avoided particularly in vulnerable patients such as the elderly. The problem therefore is not just of cost to be borne by the community, but is primarily concerned with improving the quality of therapy offered to patients.
The aforementioned so-called regional anaesthesias include, as a rule, techniques suitable for administering local anaesthetics to the spine and the nerve plexus of the upper limbs, as well as to periphery of individual nerves. Spinal techniques can be divided into epidural injection and intrathecal injection (whereby the narcotic is injected into the so-called subarachnoid space) which are both suitable for inducing, by means of a targeted anaesthetic injection into a contained spinal space, a regional anaesthesia of the lower limbs by temporarily interrupting the nervous connection between said limbs and the brain. While the intrathecal technique is more invasive than the epidural technique (in that the injection is carried out in a region deeper within the spine), it has the advantage of requiring comparatively small quantities of the anaesthetic used.
An ideal intrathecal anaesthetic for outpatient surgery use should give an immediate or at least a rapid effect (and thus have a brief onset time), should have an easily adjustable action for a predictable duration, and should exhibit low neurotoxicity as well as be without side effects.
Anaesthetics currently used for intrathecal application include lidocaine, procaine and bupivacaine, this latter being used in small doses. Unfortunately, none of the pharmacological profiles of these substances can be considered ideal. For example, news about permanent neurological damage has led to doubts suggesting the potential neurotoxicity of lidocaine (1-3). On the other hand, procaine can attain an inadequacy rate as high as 17% (4). Although bupivacaine is efficient, it can actually induce blocks whose duration in some cases is hard to predict despite the administered doses being low.
It therefore appears that none of the anaesthetics currently used for intrathecal application, in currently authorized formulations, fully satisfies all the criteria that characterize an ideal preparation. The need therefore remains to provide additional and improved compositions for intrathecal administration.
This is because a hyperbaric formulation of prilocaine authorized for intrathecal use does not currently exist.
This has not always been the case, in that a hyperbaric (thickened with glucose) 5% prilocaine solution used to be available on the English and French markets, intended for this use. This preparation actually had problems of stability over time and was withdrawn from sale because the phenomenon was never resolved. Given the obvious advantages of this active principle, other glucose-free prilocaine formulations remain available, also destined for other uses.
In view of the aforestated, the problem therefore exists of providing a stable preparation of hyperbaric prilocaine for intrathecal use, as well as a process for its preparation.